Discovery and Structural Optimization of a Novel Serine Racemase Inhibitor with a Pyridazine Skeleton
Abstract Serine racemase (SRR) inhibitors are expected to be new therapeutic agents for Alzheimer's disease. In this study, we have succeeded in discovering compound 5 , the first SRR inhibitor bearing a pyridazine ring system. We have also conducted the structure optimization of 5 and revealed a clear structure–activity relationship. Compound 5 showed about 4‐fold stronger inhibitory activity than our previously developed SRR inhibitor B and is expected to be a promising candidate compound for a new SRR inhibitor.
Authors
- Naoki Toyooka (ORCID: https://orcid.org/0000-0002-9568-1528)
- Mineyuki Mizuguchi (ORCID: https://orcid.org/0000-0003-0450-0339)
- Yuko Sakajiri
- Yoshihiro Yamanishi (ORCID: https://orcid.org/0000-0003-2279-8773)
- Hisashi Mori (ORCID: https://orcid.org/0000-0001-9743-2456)
- Takuya Okada (ORCID: https://orcid.org/0000-0003-2228-7711)
- Ryusuke Sawada (ORCID: https://orcid.org/0009-0002-5355-1204)
- Takayuki Obita (ORCID: https://orcid.org/0000-0002-9192-9362)
- Chihiro Maeda (ORCID: https://orcid.org/0000-0003-4370-3905)
- Yuki Matsukiyo (ORCID: https://orcid.org/0000-0003-0699-9970)
- Saki Oshima
- Tomokazu Shibata
- Chika Tozawa
Institutions
- Okayama University (JP)
- University of Toyama (JP)
- Nagoya University (JP)
Publication Details
- Journal
- ChemistrySelect
- Published
- 2025-09-29
- DOI
- https://doi.org/10.1002/slct.202505651
- Primary Topic
- Amino Acid Enzymes and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 0.00